The concurrent management of type 2 diabetes mellitus and heart failure presents several challenges and unmet clinical needs. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) are new generation of oral hypoglycemic agents, they inhibit renal glucose reabsorption and increase renal glucose excretion, thus lowering plasma glucose levels and contributing to a modest reduction in HbA1C. In two pivotal randomized clinical trial, SGLT2i have showed a clinically important reduction in cardiovascular mortality and hospitalization due to heart failure. However, also important adverse effects such as increased risk of bone fractures and lower limb amputations were found. Currently, physiological mechanisms leading to cardiovascular benefits with SGLT2i are not completely understood, but it seems accepted that some of these benefits are related to non-glycemic effects. In this review, we analyze the available clinical evidence focusing in cardiovascular outcomes and heart failure, physiological mechanism of action, and comment on future directions of research.

34. ClinicalTrials.gov [Internet]. Identifier NCT03036124, Study to evaluate the effect of dapagliflozin on the incidence of worsening heart failure or cardiovascular death in patients with chronic heart failure (Dapa-HF), 2017. Available from: https://clinicaltrials.gov/ct2/show/NCT03036124?term=NCT03036124&rank=1.